1. Field of the Invention
The present invention relates to the field of pharmaceutical compositions comprising a synergistic combination of trimethoprim and sodium sulfacetamide. More particularly, this invention relates to aqueous preparations containing trimethoprim and sodium sulfacetamide, wherein the trimethoprim has been solubilized by the sodium sulfacetamide. These preparations are particularly well-suited for ophthalmic or otic use.
2. Discussion of Related Art
It is known that trimethoprim, which is classified as a benzylpyrimidine, potentiates the antimicrobial activity of sulfonamides (e.g., sulfamethoxazole). Synergistic combinations of trimethoprim and one or more sulfonamides have been used extensively in the treatment of bacterial infections, particularly systemic infections and infections of the urinary tract. Reference is made to the following publications for further background regarding such compositions: U.S. Pat. Nos. 3,515,783; 3,551,564; 4,303,643; 4,332,796; and 4,386,084.
There have been two significant problems associated with prior art attempts to formulate aqueous pharmaceutical preparations containing either trimethoprim or a combination of trimethoprim and one or more sulfonamides. First, it is well known that trimethoprim has a tendency to form insoluble complexes when combined with sulfonamides in aqueous media. The poor aqueous solubility of trimethoprim represents a second significant problem associated with formulation of such solutions. Prior attempts to address these problems are described in the following patent publications: U.K. Patent Application GB 2,073,587A; U.K. Patent Specification 1,582,692; U.S. Pat. No. 3,985,873; and U.S. Pat. No. 3,985,876. The U.K. patent publications describe the use of aldehydes and high concentrations of polyvinylpyrrolidone, respectively, as solutions to the above-cited formulation problems. U.S. Pat. No. 3,985,873, proposes the use of water soluble mono salts of trimethoprim to overcome the aqueous solubility problem mentioned above. As a means for avoiding the complexation problem mentioned above, U.S. Pat. No. 3,985,876, proposes the use of water-miscible organic solvents to solubilize sulfonamides in combinations of sulfonamides and sulfonamide potentiators (e.g., trimethoprim).